The Expression And Correlation Of SIRT1and Phospho-SIRT1in Colorectal Cancer

Backgrounds:Silent information regulator2(Sir2) is an anti-aging gene that was originallydiscovered in budding yeast, which encodes a small protein sirt2with NAD+dependenthistone deacetylase activity. SIRT1is a homology analogy of sirt2in mammals, whichinvolved in cell energy metabolism, proliferation, senescence, multiple inflammatoryprocesses, neuroprotection, tumorigenesis and so on, by deacetylating multipletranscription factors. However, there are many controversies on the function of SIRT1intumorigenesis——SIRT1is a tumor promoter or tumor suppressor? SIRT1locates in thenucleus or cytoplasm? Until now, the specific mechanism of SIRT1is unclear, so furtherstudy need to be down.Some studies have reported that the phosphorylation can regulate the activity ofSIRT1deacetylation and nucleocytoplasmic shuttling. However, researches on Phospho-SIRT1in tumors are relatively rare, so we focused on the expression and subcellularlocalization of Phospho-SIRT1in colorectal cancer.Objectives:1. To investigate the expression and subcellular localization of SIRT1andPhospho-SIRT1in colorectal cancer tissues and normal tissues.2. To investigate the expression of SIRT1mRNA in colorectal cancer tissues andcorresponding normal tissues.3. To investigate the possible correlations between SIRT1or Phospho-SIRT1expression and clinicopathological features.4. To investigate the possible correlations between Phospho-SIRT1and SIRT1.5. To explore the role of phosphorylation in colorectal cancer. Methods:1. Immunohistochemical staining and Western blot were performed to detect theexpressions and subcellular localization of SIRT1and Phospho-SIRT1in colorectal cancertissues and corresponding normal tissues.2. Real-Time PCR was performed to detect the expression of SIRT1mRNA incolorectal cancer tissues and corresponding normal tissues.Results:1. SIRT1was completely localized in the nucleus and was highly increased incolorectal cancer tissues. SIRT1overexpression in tumor tissues was associated withyounger age, advanced TNM stage and mutant P53loss.2. Phospho-SIRT1was completely localized in the nucleus and was highly increasedin colorectal cancer tissues. Phospho-SIRT1overexpression in tumor tissues wasassociated with Ki67.3. Phospho-SIRT1and SIRT1expression in colorectal cancer was positivelycorrelated. The ratio of Phospho-SIRT1and SIRT1was higher in cancer tissues than innormal tissues.4. SIRT1mRNA was no significant difference in colorectal cancer tissues and normaltissues.Conclusions:1. SIRT1was overexpressed in colorectal cancer tissues, which associated withyounger age, advanced TNM stage and mutant P53loss, indicating that SIRT1is a bothfavorable and unfavorable clinicopathological index. SIRT1may be as a tumor promoter ortumor suppressor.2. Phospho-SIRT1was overexpressed in colorectal cancer tissues, which associatedwith Ki67, indicating that Phospho-SIRT1may be involved in tumor formation.3. Phospho-SIRT1and SIRT1expression in colorectal cancer was positivelycorrelated. The ratio of Phospho-SIRT1and SIRT1was higher in cancer tissues, suggestingPhospho-SIRT1may determine the role of SIRT1in colorectal cancer.4. SIRT1and Phospho-SIRT1are both located in the nucleus, without cytoplasmlocalization. This research cannot demonstrate the nucleocytoplasmic shuttling of SIRT1.5. Changes in SIRT1protein levels are not associated with changes in SIRT1mRNAtranscriptional levels, suggesting post-transcription may play an important role in SIRT1regulation.